Critical hydrogen bonding by serine 235 for cephalosporinase activity of TEM-1 beta-lactamase.

Abstract:

:The role of Ser-235 in the catalytic mechanism of the TEM-1 beta-lactamase has been explored by the study of a mutant enzyme in which Ser-235 has been substituted by alanine (Ala-235 mutant enzyme). A comparative kinetic analysis of both the wild-type and the Ala-235 TEM-1 enzymes revealed little effect of this substitution of residue 235 on the turnover of penicillins but a greater effect on the turnover of cephalosporins. Susceptibility testing of Escherichia coli strains harboring the wild-type TEM-1 beta-lactamase and the Ala-235 mutant enzyme revealed an effect of the mutation similar to that observed in the enzymological studies. The MICs of two representative cephalosporins for the strain containing the mutant enzyme were much lower than those for the isogenic strain bearing the wild-type TEM-1 beta-lactamase. On the other hand, the strain with the mutant enzyme was still highly resistant to penicillins.

authors

Imtiaz U,Manavathu EK,Lerner SA,Mobashery S

doi

10.1128/aac.37.11.2438

subject

Has Abstract

pub_date

1993-11-01 00:00:00

pages

2438-42

issue

11

eissn

0066-4804

issn

1098-6596

journal_volume

37

pub_type

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